216 - When Hope Becomes Hazard: Severe Dual-Organ Toxicity from the First FDA-Approved Friedreich's Ataxia Treatment

Friday, February 20, 2026

5:00 PM - 6:30 PM AST

Presenting Author(s)

CF

Chase Forbes, BA

Medical Student
PCOM Georgia
Lawrenceville, Georgia, United States
ZS

Zachary Shumaker, MD

Medical Resident
Atrium Health
Charlotte, North Carolina, United States

Co-Author(s)

MO

Michael Ortiz, MD

Physician
Atrium Health
Charlotte, North Carolina, United States

Submitter(s)

ZS

Zachary Shumaker, MD

Atrium Health
Charlotte, North Carolina, United States

Case Diagnosis: Severe dual organ toxicity from omaveloxolone rechallenge in Friedreich's Ataxia

Case Description: A 34-year-old male with Friedreich's Ataxia (FA) developed mild hepatotoxicity with ALT of 55 after an initial trial of omaveloxolone, the sole FDA-approved therapy for FA, prompting discontinuation. Given the lack of alternative FA treatment options, the patient and his family decided to retrial omaveloxolone. Six weeks into the retrial, he presented with emergency department with severe hepatotoxicity (ALT 5,601, AST 5,195), acute cardiomyopathy (EF 65%→20-25%), and gastrointestinal symptoms. His course was complicated by heart failure, atrial fibrillation, shock, and diabetic ketoacidosis. Omaveloxolone was permanently discontinued, and the patient required intensive treatment including N-acetylcysteine, insulin, heart failure therapy, and antibiotics. Remarkably he achieved complete normalization of ALT and AST with a return to normal cardiac ejection fraction. Despite resolution of organ failure and significant functional improvement during inpatient rehabilitation, the patient demonstrated a persistent functional decline relative to his pre-omaveloxolone baseline, necessitating ongoing increased assistance with mobility and transfers.

Discussions: This case represents the first reported omaveloxolone-induced dual-organ toxicity involving both hepatotoxicity and cardiomyopathy. Rechallenge after mild initial hepatotoxicity led to 100-fold increase in ALT and AST levels alongside cardiomyopathy, however, even with resolution of these symptoms, functional limitations including increased required assistance and heightened fall risk persisted as potential long-term outcomes. This case demonstrates the necessity to closely monitor cardiac and hepatic function throughout medication trial.

Conclusions: This case underscores omaveloxolone's potential for severe cardiomyopathy and hepatotoxicity necessitating vigilant cardiac and hepatic monitoring during administration for Friedreich's ataxia treatment. The patient's full recovery from organ dysfunction is encouraging. Physicians and patients alike should be reassured that full resolution of organ toxicity is possible. However, persistent functional deficits should be recognized as possible consequences of omaveloxolone trials.